The overall objectives of this proposal are to use highly purified and well characterized membrane derived molecules to elucidate the functional role of the membrane in the generation and control of the immune response. The characterization of the membrane expression of antigens, the chemical structure of surface antigens and the cell biology of their anchorage and shedding will be performed in conjunction with parallel studies of the functional role of membrane antigens in normal and aberrant immune responses. Research plans can be divided into three basic areas. These are: 1) the structural analysis and characterization of Thy-1 and other glycolipid and glycoprotein antigens of lymphoid cells; 2) the membrane aspects of antigen expression including important factors in the production, transport, cell surface exposure, the shedding and release of membrane complexes; and 3) the functional aspects of released shed membrane complexes. The first part of this study will utilize both lymphoid (stimulated T cell, lymphoma and later hybridoma) and neural sources of Thy-1 antigen. The objective of this phase is the characterization of glycolipid and glycoprotein antigens which carry Thy-1 antigenicity and other antigenic determinants of receptor activity. The second part of this study will utilize bone marrow cells, T cell lymphoma cell lines and eventually T cell hybridoma lines. The third part of this study will utilize various immunological assays to which isolated antigens or shed complexes will be added to assess their potential immunological function. The proposed study will increase our understanding of membrane phenomena especially as they relate to the control of the immune response to tumor cells, allograft cells and in autoimmune and immunodeficiency states.